β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals.

Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group ( n = 15 ) and treatment group ( n = 15 ). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed ( p > 0.05 ). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA ( p < 0.05 ), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.

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Tax is a financial charge imposed on individuals by state in different forms like direct tax paid directly by individuals, indirect tax collected by intermediaries and deposited to Government like sales tax. Taxation plays an important role in the process of revenue generation and to run various activities in an economy. The study empirically demonstrates various factors involved in direct and indirect tax collection in Pakistan. Tax to GDP ratio, corruption, political instability, trade openness, real per capita income and inflation were considered main factors affecting tax collection in empirical testing. Corruption and political instability were measured by using corruption index and political instability index respectively. Time series data from 1980-2010 was used for regression analysis. Data of all variables was obtained from International Country Risk Guide (ICRG), Handbook of Statistics and Polity to Project IMF. Augmented Dickey Fuller (ADF) test was applied to check the stationarity of all variables. Autoregressive Distributed Lagged (ARDL) model was applied to find out long run and short run dynamics of models. The results indicated tax collection shrinks due to increasing corruption, inflation and political instability while trade openness and real per capita income boost tax revenues. The study suggested important policy implication for increasing tax collection in Pakistan.

Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in β-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with β-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were altered before HU therapy at p ≤ 0.05 and fold change >2.0 in β-thalassemia patients; started reverting towards healthy group after HU treatment. A prediction model based on another set of 70 HU treated patients showed a good separation of GR from untreated β-thalassemia patients with an overall accuracy of 76.37%. Metabolic pathway analysis revealed that various important pathways that were disturbed in β-thalassemia were reverted after treatment with HU and among them linoleic acid pathway was most impactfully improved in HU treated patients which is a precursor of important signaling molecules. In conclusion, this study indicates that HU is a good treatment option for β-thalassemia patients because in addition to reducing blood transfusion burden it also ameliorates disease complications by shifting body metabolism towards normal.